eprints.soton.ac.uk€¦ · web view3 nihr southampton biomedical research centre, university of...

Maternal stress and psychological distress preconception: association with offspring

atopic eczema at age 12 months.

El-Heis S 1 , Crozier SR1, Healy E2, Robinson SM1,3, Harvey NC1,3, Cooper C1,3,4, Inskip HM1,3,

Baird J1,3, Southampton Women’s Survey Study Group, Godfrey KM1,3,5

1 Medical Research Council Lifecourse Epidemiology Unit, University of Southampton, UK

2 Dermatopharmacology, Faculty of Medicine, University of Southampton, UK

3 NIHR Southampton Biomedical Research Centre, University of Southampton and University

Hospital Southampton NHS Foundation Trust, Southampton, UK

4 NIHR Musculoskeletal Biomedical Research Unit, University of Oxford, Oxford, UK

5Institute of Developmental Sciences, University of Southampton, Southampton, UK.

Correspondence to:

Professor Keith Godfrey

Medical Research Council Lifecourse Epidemiology Unit (University of Southampton)

Southampton General Hospital, Mail point 95

Southampton SO16 6YD

United Kingdom.

Tel: 44 (0)23 80777624

Fax: +44 (0)23 80704021

Email: [email protected]

Key words: Atopic eczema, maternal stress, maternal mood.

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Abbreviations: GHQ (General Health Questionnaire), EPDS (Edinburgh Postnatal Depression

Scale), OR (Odds Ratio), HPA (Hypothalamic-Pituitary-Adrenal), Th1 and 2 (T-helper), IL

(Interleukin), SWS (Southampton Women’s Survey), SF-36 (Short Form (36) Health

Questionnaire), PHQ9 (Patient Health Questionnaire), DAG (Directed Acyclic Graph), SD

(Standard Deviation), CRH (Corticotropin Releasing Hormone)

Word count: 3013

Table and figure count: 7

Short running title: Maternal stress/psychological distress preconception and offspring

atopic eczema.

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Abstract

Background: Perinatal maternal stress and low mood have been linked to offspring atopic

eczema.

Objectives: To examine the relation of maternal stress/mood with atopic eczema in the

offspring, focusing particularly on stress/psychological distress preconception.

Methods: At recruitment in the UK Southampton Women’s Survey, preconception maternal

reports of perceived stress in daily living and the effect of stress on health were recorded; in

a sub-sample psychological distress was assessed (12-item General Health Questionnaire).

Infants were followed up at ages 6 (n=2956) and 12 (n=2872) months and atopic eczema

ascertained (based on UK Working Party Criteria for the Definition of Atopic Dermatitis). At

6 months postpartum, mothers were asked if they had experienced symptoms of low mood

since childbirth and completed the Edinburgh Post-natal Depression Scale.

Results: Preconception perceived stress affecting health (OR 1.21 (95%CI 1.08-1.35),

p=0.001) and stress in daily living (OR 1.16 (1.03-1.30), p=0.014) were associated with an

increased risk of offspring atopic eczema at age 12 months but not at 6 months, robust to

adjustment for potentially confounding variables. Findings were similar for maternal

psychological distress preconception. Low maternal mood between delivery and 6 months

postpartum was associated with an increased risk of infantile atopic eczema at age 12

months, but no significant association between postnatal mood and atopic eczema was seen

after taking account of preconception stress.

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Conclusion & Clinical Relevance: Our data provide novel evidence linking maternal stress at

preconception to atopic eczema risk, supporting a developmental contribution to the

aetiology of atopic eczema and pointing to potentially modifiable influences.

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Introduction

Atopic eczema is a prevalent chronic skin condition that can have a considerable impact on

quality of life and a significant financial burden. A rise in prevalence has been observed

globally [1], with an estimated annual prevalence of 9.5% in children under 4 years of age in

the UK [2]. There is increasing evidence that atopic eczema partly originates in utero, where

genetic susceptibility and environmental exposures can result in immune dysregulation [3],

influencing the risk of developing the condition. Better understanding of such early life

environmental exposures could help identification of preventative strategies.

Pathways by which maternal stress can cause fetal immune dysregulation leading to a

propensity to develop atopic eczema and other atopic disorders have been proposed. In

mice, transplacental passage of maternal stress hormones affects fetal hypothalamic-

pituitary-adrenal (HPA) axis development, with prenatally stressed offspring demonstrating

airway inflammation and hyper-responsiveness [4]. Maternal stress also alters placental

corticotrophin releasing hormone (CRH) regulation, with the potential to influence the fetal

HPA axis [5]. In addition, glucocorticoids and catecholamines released as a result of stress

can modulate differentiation of type 1 and 2 T-helper (Th1 and Th2) cells, favouring a shift

towards a Th2 humoral cell type reaction with overproduction of interleukins 4 and 10 and

suppression of interleukin 12 [6]. This inflammatory reaction is seen in atopic eczema and

other atopic conditions.

Experimental studies in rodents and sheep have shown that maternal glucocorticoid

exposure during the period around conception can have important effects on a range of

organs, including the HPA axis, with implications for immune disorders such as atopic

eczema [7, 8]. In humans the consequences of stress around conception remain

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underexplored. In a recent systematic review, Andersson et al [9] identified a number of

studies linking prenatal maternal stress to an increased risk of offspring atopic eczema [10-

14]. Sausenthaler et al. [13] observed a link between maternal stress during pregnancy and

an increased risk of atopic eczema in the first 2 years of life but not beyond that age as a

result of stress during pregnancy, suggesting that the impact of prenatal stress weakens in

the presence of other influencing factors. When examining other atopic disorders in relation

to prenatal maternal stress, De Marco et al. [12] reported comparable odds ratios for

asthma, eczema and allergic rhinitis, supporting an immunomodulatory effect of stress and

stress hormones on the development of atopy in humans. Furthermore, postpartum

depression during the first 6 months of life has been linked with childhood atopic eczema at

age 3 years, independently of prenatal maternal stress [15]. Early life persistent and

increasing maternal postnatal depressive symptoms [16, 17], greater caregiver perceived

stress [18], and prenatal and postnatal negative life events [19] have also been associated

with an increased risk of offspring asthma.

It is possible that mothers experiencing stress may make poor health practice choices,

including smoking, or differ in terms of their age, educational attainment, parity and history

of eczema, which put their offspring at an increased risk of developing atopic eczema [20],

and thus previous studies may not have controlled for all potential confounding variables.

Moreover, no previous studies have explored the link between maternal preconception

stress/ low mood and offspring risk of developing atopic eczema.

The objective of this study was to determine whether the risk of developing infantile atopic

eczema at ages 6 and 12 months was influenced by maternal stress and low mood,

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controlling for a range of potential confounding factors and with particular focus on the

effects of stress prior to conception.

Methods

Southampton Women’s Survey

In the UK Southampton Women’s Survey (SWS), between 1998 and 2002, 12,583 women

aged 20-34 years who were not pregnant were recruited from the general population

through general practitioners in Southampton, UK, and the surrounding area. Information

on maternal diet, lifestyle, socioeconomic status, stress and psychological distress was

collected [21]. Women who became pregnant were followed up through their pregnancies;

3158 live born infants were delivered. The findings reported in this manuscript are based on

the 3008 mother-offspring dyads assessed for atopic eczema at 6 and/or 12 months. All

phases of the Southampton Women’s Survey were approved by the Southampton and

South West Hampshire Local Research Ethics Committee and parents gave written informed

consent.

Stress and mood assessments

At recruitment (preconception) women were asked to report perceived stress using two

questions (‘To what extent do you feel that the stress or pressure you have experienced in

your life has affected your health?’ (n=3002), and ‘In general, how much stress or pressure

have you experienced in your daily living in the last 4 weeks?’(n=3007)), grading the impact

of stress into one of five groups (none, slightly/just a bit, moderately/a good bit, quite a lot,

extremely/a great deal). These were adapted from the Short Form (36) Health Survey (SF-

36) [22]. A subgroup of participants also completed the 12 item General Health

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Questionnaire (GHQ-12) (n= 1729) assessing mental wellbeing, in which a score of ≥3 is

considered indicative of psychological distress [23].

At 6 months postpartum, mothers completed the Edinburgh Post-natal Depression Scale

(EPDS), where higher scores indicate lower mood and a score of 13 or more is considered

indicative of probable major depression [24]. A subgroup of mothers (n=1660-1713) were

also asked if they had experienced symptoms of low mood between delivery and infant age

6 months (episodes of feeling sad, depressed or gloomy for most of day, unable to find

pleasure in things normally enjoy, lost interest in things normally enjoy, feeling tired or worn

out and episodes of having less energy than usual), these questions were adapted from the

Patient Health Questionnaire- 9 (PHQ-9) [25].

Outcome assessment

Case definition of atopic eczema was based on the UK Working Party diagnostic criteria for

the definition on atopic eczema [26]; as assessed by trained research nurses who

administered a standardised questionnaire and ascertained other information required for

the diagnostic criteria (a combination of history of itchy skin condition and two of the

following: history of involvement of the skin creases such as folds of elbows, behind the

knees, fronts of ankles, cheeks or around the neck, a history of a general dry skin in the last

year and visible flexural eczema or eczema involving the cheeks/forehead and outer limbs

in). All infants were assessed for eczema before the age of 2 years, thus this criterion was

met by all infants in the study cohort. However, as the infants were not old enough to have

developed clearly defined atopic disorders, a personal history of atopy was omitted as a

criterion.

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Statistical analysis

Confounding variables were determined prior to the analysis using a directed acyclic graph

(DAGs) (Supplementary figure 1) [27]. Maternal factors that were included as potential

confounding variables in our analyses were age at child’s birth, education, smoking, parity

and eczema in the past 12 months; infant confounding variables were infant sex, gestational

age, season of birth and breastfeeding. P values < 0.05 were considered statistically

significant. Data on maternal and paternal eczema in childhood were available for most of

the cohort, and additional analyses controlling for these were undertaken and are shown in

supplementary tables 1 and 2. Logistic regression analyses were performed (Stata version

14.1, Statacorp LP, TX) to relate maternal stress/mood to infant atopic eczema at ages 6 and

12 months. The five-category variables describing stress preconception were analysed as

continuous variables.

Further logistic regression models were used to analyse the relations between

preconception stress (as determined by stress affecting health and stress in daily living) and

postnatal low mood (as determined by EPDS score) and infant atopic eczema at ages 6 and

12 months. GHQ-12 scores and postnatal symptoms of low mood were not included in this

analysis as these were only assessed in subsets of the study population.

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Results

Cohort characteristics

Maternal and infant characteristics are summarised in Table 1. Among the study group, the

mothers’ average age at their children’s birth was 30.7 years (standard deviation (SD) = 3.8);

51.4% were primiparous, 15.7% smoked during pregnancy and 7.0% of the mothers had

eczema in the past 12 months. The mean duration between the initial questionnaire and

conception was 2.2 years. 51.9% of infants were male; mean birthweight of infants was 3.44

kg (SD 0.55) and gestational age 40.1 weeks (IQR 39.0-41.0). 2956 infants were assessed for

eczema at age 6 months, 8.9% of which had atopic eczema. At age 12 months 2872 infants

were assessed and 9.4% had atopic eczema.

Table 2 provides descriptive data on maternal mood. Preconception, 28.2% had a GHQ-12

score of ≥3, suggestive of psychological distress; 17.7% reported that stress affected their

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health ‘quite a lot’ or ‘extremely’ preconception and 24.6% reported ‘quite a lot’ or ‘a great

deal’ of stress experienced in daily living. At 6 months after delivery, 46.8% reported

episodes of feeling sad, depressed or gloomy for most of the day; the median EPDS score

was 10 (IQR 6-15) and 36.7% had a score of 13 or more.

Association between maternal stress and mood and infant atopic eczema at age 6 months

Table 3 shows univariate (unadjusted) and multivariate (adjusted) analyses of maternal and

infant characteristics in relation to infant atopic eczema at age 6 months. Stress in daily

living preconception was associated with increased risk of offspring atopic eczema (OR 1.13,

95% CI 1.01-1.28, p = 0.039); this association weakened slightly after adjusting for potential

confounders (adjusted OR 1.12, 95% CI 0.99-1.28, p=0.072). Episodes of feeling sad,

depressed or gloomy for most of the day experienced between delivery and infant age 6

months were associated with an increased risk of atopic eczema after taking confounding

variables into account (OR 1.40, 95%CI 1.00-1.96, p= 0.048). Other measures of maternal

postnatal mood and postnatal EPDS score were not associated with offspring atopic eczema

at age 6 months. Additionally controlling for maternal and paternal eczema in childhood had

little effect on the 6 month eczema analyses shown in Table 3 (Supplementary Table 1).

Association between maternal stress and mood and infant atopic eczema at age 12 months

Table 4 shows similar analyses in relation to infant atopic eczema at age 12 months.

Psychological distress ascertained by the GHQ-12 preconception was associated with

increased risk of atopic eczema (OR 1.43, 95% CI 1.00-2.04, p = 0.044), but the association

weakened slightly after adjusting for confounding variables (OR 1.37, 95% CI 0.93-2.00, p =

0.11). Increased stress in life affecting health (OR 1.21, 95% CI 1.08-1.35, p = 0.001, Figure 1)

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and increased stress in daily living (OR 1.16, 95%CI 1.03-1.30, p = 0.014, Figure 2)

preconception were associated with an increased risk of offspring atopic eczema at age 12

months, these associations remaining significant after adjusting for confounding variables (p

= 0.014 and p = 0.046, respectively). Examining postnatal maternal mood, all five measures

(experiencing episodes of feeling sad, depressed or gloomy for most of the day unable to

find pleasure in things normally enjoyed, loss of interest in things normally enjoyed, having

less energy than usual) ascertained 6 months after delivery showed associations or trends

towards lower maternal mood being associated with a higher odds of offspring atopic

eczema at age 12 months in both unadjusted and adjusted analyses (p = 0.08 to p = 0.013);

adjusting for potential confounders generally increased the odds ratios of atopic eczema. A

higher EPDS score examined as a continuous variable was also significantly associated with

increased risk of atopic eczema at 12 months (OR 1.02, 95%CI 1.00-1.04, p = 0.045), but

there was no association with an EPDS score of ≥13. Additionally controlling for maternal

and paternal eczema in childhood somewhat attenuated the association with maternal

preconception stress in daily living in the past 4 weeks (adjusted OR 1.10, 95%CI 0.97-1.25, p

= 0.14), with little effect on the associations with preconception stress in life affecting health

or postnatal stress variables shown in Table 4 (Supplementary Table 2 ).

Sensitivity analysis indicated that infants of women who reported greater perceived stress

affecting health and stress in daily living and were conceived less than 1 year after the

mother completed the initial preconception assessment had higher odds of developing

atopic eczema at age 12 months compared with the offspring whose mothers did not report

stress; this effect was greater than that seen among women in the whole study cohort (ORs

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of 1.25 vs 1.21 for stress affecting health, 1.22 vs 1.14 for stress in daily living for adjusted

analyses) (Supplementary Table 3).

We undertook further multivariate analyses to examine the relation of offspring atopic

eczema with preconception stress as determined by perceived stress affecting health and

stress in daily living, and postnatal low mood as determined by EPDS (Table 5). Examining

atopic eczema at age 6 months; we found no association with stress/low mood either

preconception or postnatally. However, examining atopic eczema at age 12 months; stress

affecting health at preconception (p= 0.015) was associated with an increased risk of atopic

eczema but no significant association was seen between postnatal mood and eczema after

taking account of preconception stress/mood variables.

A sensitivity analysis omitting 52 infants who had questionnaire data but missing data on

visible eczema that could potentially have contributed to the case definition of atopic

eczema (52 infants at age 6 months, 5 infants at age 12 months) showed little change in

relation to the findings for either 6 month eczema and perceived stress in life affecting

health (OR 1.11, 95% CI 0.99-1.25), perceived stress affecting daily living in the past 4 weeks

(OR 1.13, 95% CI 1.01-1.28) and EPDS (OR 1.01, 95% CI 0.99-1.03) or 12 month eczema and

the same variables OR 1.21 (95% CI 1.08-1.36), 1.16 (95% CI 1.03-1.30) and 1.02 (95% CI

1.00-1.04), respectively.

Discussion

We found that maternal preconception stress was associated with an increased risk of

offspring atopic eczema at age 12 months but not at age 6 months. These associations were

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robust to adjustment for potentially confounding variables including maternal history of

eczema in the past 12 months, maternal smoking during pregnancy, infant gestational age,

sex and breastfeeding duration. Findings were similar for maternal psychological distress

preconception. Low maternal mood between delivery and 6 months postpartum assessed

using the EPDS as a continuous variable (but not as a dichotomous variable) was also

associated with an increased risk of infantile atopic eczema at age 12 months, but no

significant association between postnatal mood and eczema was seen after taking account

of preconception stress/mood variables. There are many research papers utilizing EPDS as a

continuous scale in relation to different outcomes. [28, 29] Using the EPDS as a continuous

outcome better captures the multiple dimensions ascertained by the questionnaire,

including anxiety, low mood and a sense of helplessness [30], which may not be captured by

dichotomising the score (as used in clinical practice to screen for depression).

Maternal stress in the prenatal [9] and postnatal [15] periods have previously been shown to

be linked to offspring atopic eczema. Our data, however, are the first to show a link

between maternal stress preconception and the risk of this skin disorder.

Previous research has examined potential mechanisms for maternal prenatal stress resulting

in effects in the fetus (which might lead to atopy in the offspring). For example, stress is

associated with raised cortisol levels and although the majority of the maternal cortisol is

metabolised as it crosses the placenta, 10-20% can pass through the placenta un-

metabolised; this amount can double the much lower fetal cortisol concentration, and a

linear relationship between fetal cortisol concentration and maternal cortisol concentration

has been observed [31]. Placental CRH (pCRH) which is also released as a result of maternal

stress, creates a positive feedback loop and a subsequent increase in pCRH, ACTH and

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cortisol. pCRH affects both mother and fetus and has been shown to impact fetal

programming and influencing health outcomes [32]. Furthermore, mothers experiencing

psychosocial stress or nervousness during pregnancy have been found to have raised

maternal serum pro-inflammatory cytokines [33] and higher umbilical cord IgE

concentrations [34], respectively. Despite maternal neuroendocrine changes occurring as

part of pregnancy, maternal psychosocial status has also been linked with circulating plasma

levels of neuroendocrine parameters including ACTH, B-endorphin and cortisol [35]. Chang

et al proposed a further potential mechanism linking maternal stress with increased

offspring susceptibility to atopic eczema where the placenta fails to maintain its detoxifying

ability when reactive oxygen species are high during stress, exposing the developing foetus

to oxidative stress [36].

The stress model is complex and has evolved in recent years with some studies exploring the

link between atopic eczema and certain aspects of this model including exposure to

stressors, such as significant life events, perceived stress and stress related disorders

including anxiety and depression prenatally. Wen et al reported that self-reported

psychological distress in the third trimester, cord blood IgE and lymphotoxin (LT-α) and high-

affinity receptor for IgE (FcεRI-β) genotypes were associated with offspring atopic eczema at

2 years of age [10]. Children of mothers who experienced stressful life events (divorce,

mourning, loss of job) during pregnancy were found to have a moderately increased risk of

atopic eczema, wheezing, asthma and allergic rhinitis [12]. Hartwig et al [11] observed

similar associations where a higher likelihood of atopic asthma and eczema in 14 year olds

was seen in those whose mothers experienced negative life events in the second half of

pregnancy.

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Physiological responses to acute and chronic stress differ. The release of stress hormones in

adaptation to acute stress in order to maintain homeostasis is referred to as allostasis [37].

Increased allostatic load develops as a result of recurring exposure to stress, protracted

response to stress and incapability to adapt [38]. Although the nature, severity, significance

and persistence of stress are important [39], personality traits, coping ability and physical

stress are also influential in the way humans respond to stress and this makes quantifying

stress difficult. As a result, detailed understanding of the exact amount of stress experienced

personally by each individual, and the effects of that stress on biological events, is limited.

Exposure to stress during sensitive stages of development in early life can affect the

programming of the HPA axis through epigenetic changes and may result in a Th2 dominant

immune response [40]. Also, methylation of the gene encoding the glucocorticoid receptor

(NR3C1) has been shown to be associated with exposure to prenatal psychological distress

[41]. The stages that are most sensitive to immunomodulatory effects of maternal stress

have not been identified. Evidence from animal studies support the notion that maternal

exposure to stress such as undernutrition around conception [7, 8, 42, and 43] and stress

such as restraint and noise and light stress in early pregnancy can affect the development of

a number of systems, including the immune system and the HPA axis [44, 45]. However,

evidence is scarce on the impact of periconceptional stress on HPA development in humans.

Furthermore, it is unclear whether neuroendocrine changes related to maternal stress

occurring around the time of conception influence the risk of atopic eczema in the same

mechanistic way as if they occurred later in pregnancy.

We found that maternal stress was associated with infant eczema at age 12 months but not

at age 6 months; this could reflect heterogeneity in the aetiology and pathogenesis of atopic

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eczema in early childhood [46]. Our data are consistent with these observations, where

atopic eczema occurring in late infancy was associated with environmental factors and

atopic eczema with an early onset in the first six months was mainly associated with familial

factors [46]. We showed that infants conceived within 1 year of their mothers reporting

increased stress affecting health and stress in daily living had higher odds of developing

atopic eczema when compared with the remainder of the study cohort, suggesting that

stress/low mood experienced closer to the time of conception may have a greater impact on

the risk offspring atopic eczema.

Our study highlights a link between maternal stress at preconception and an increased risk

of atopic eczema in the offspring at 12 months. Strengths of the study are its large sample

size, its prospective nature, collection of true preconception data, the standardised

assessment of eczema by trained staff and control for confounding factors. The questions on

perceived stress in daily living and stress affecting health preconception were directly

adapted from the Short Form (36) Health Survey, which is an established research tool for

ascertaining perceived stress [22]. The General Health Questionnaire (GHQ-12) is likewise, a

widely utilized standard questionnaire assessing mental wellbeing, which has been validated

as measuring psychological distress [23]. Nevertheless, limitations were the lack of

evaluation of stress during pregnancy and the use of questionnaire-based assessments of

stress where there is potential for reporting bias. A further limitation is that 52 infants at

age 6 months and 5 infants at age 12 months had missing information on visible eczema

that could potentially have contributed to the case definition of atopic eczema; however, a

sensitivity analysis omitting these infants with a missing skin examination information

showed little change in the findings. Bioindicators relating to stress were not collected;

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however, indicators such as salivary cortisol may be difficult to interpret as concentrations

fluctuate, particularly during pregnancy.

In summary, our study demonstrates a novel link between preconception maternal stress /

low mood and the risk of atopic eczema in the offspring. The findings point to potentially

modifiable maternal influences on this complex, multifactorial skin condition and add to the

evidence that atopic eczema partly originates during development before birth.

Funding

This work was supported by grants from the Medical Research Council, British Heart

Foundation, Food Standards Agency, Arthritis Research UK, National Osteoporosis Society,

International Osteoporosis Foundation, Cohen Trust, European Union's Seventh Framework

(FP7/2007-2013), projects EarlyNutrition and ODIN under grant agreement numbers 289346

and 613977, NIHR Southampton Biomedical Research Centre, University of Southampton

and University Hospital Southampton NHS Foundation Trust, NIHR Musculoskeletal

Biomedical Research Unit, University of Oxford and British Lung Foundation.

Author contributions

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The authors’ responsibilities were as follows—KMG, HMI, SMR, JB, NCH, and CC: were

responsible for the design and conduct of the Southampton Women's Survey; with input

from SRC and EH, SEH and KMG planned the analyses and drafted the manuscript; SEH:

conducted the statistical analyses with support from SRC; and all authors: read and

approved the final version of the manuscript.

Conflict of interest

KMG has received reimbursement for speaking at conferences sponsored by companies

selling nutritional products and is part of an academic consortium that has received research

funding from Abbott Nutrition, Nestec, and Danone. No other author reports any potential

conflicts of interest.

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Table 1. Characteristics of the study population

Total n n (%), Median (IQR) or Mean (SD)

MaternalAge at child’s birth (y) 3008 30.7 (3.8)

% A level or higher 2999 59.1%

% Smoking in pregnancy 2870 15.7%

% Primiparous 3005 51.4%

% Eczema in last 12 months 2815 7.0%

Infant% Male 3008 51.9%Gestational age (weeks) 3008 40.1 (39.1-41.0)

Birthweight (kg) 2981 3.44 (0.55)

Born in winterBorn in springBorn in summerBorn in autumn

673726807802

22.4%24.1%26.8%26.7%

Breast feeding (completed months)Never breast fed <11 to 34 to 67 to 1112 or more

527581615484422241

18.4%20.2%21.4%16.9%14.7%8.4%

6 month assessmentAge (wks) 2956 27.4 (26.1-33.7)

% Atopic eczema as per UK working party criteria

2956 262 (8.9%)

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12 month assessmentAge (wks) 2872 53.7 (52.6-55.0)

% Atopic eczema as per UK working party criteria

2872 270 (9.4%)

Table 2. Descriptive data of maternal mood

Total n n (%) or Median (IQR)

PRECONCEPTION

Maternal stress preconceptionStress in life affecting health 3007

None 723 (24.0%)Slightly 1203 (40.0%)Moderately 548 (18.2%)Quite a lot 448 (14.9%)

Extremely 85 (2.8%)Stress in daily living in last 4 weeks 3002

None 248 (8.3%)Just a bit 1373 (45.7%)A good bit 644 (21.5%)Quite a lot 572 (19.1%)

A great deal 165 (5.5%)

Maternal mental wellbeing preconceptionPsychological distress ascertained by General Health Questionnaire

1729

No (score <3) 1241 (71.8%)Yes (score ≥3) 488 (28.2%)

POSTNATALMaternal mood in worst 2 week period between birth and infant age 6 monthsEdinburgh Postnatal Depression Score 2853 10 (6-15)

Edinburgh Postnatal Depression Score ≥13 1046 (36.7%)Postnatal maternal mood between delivery and infant age 6 months

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Between delivery and infant age 6 months experienced episodes of:Feeling sad, depressed or gloomy for most of day 1713 802 (46.8%)Unable to find pleasure in things normally enjoy 1660 502 (30.2%)Lost interest in things normally enjoy 1660 490 (29.5%)Feeling tired of worn out 1660 1319 (79.7%)Less energy than usual 1660 1294 (78.0%)

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Table 3. Maternal stress/mood preconception and postnatally in relation to infant atopic eczema at age 6 months.

Unadjusted Adjusted *

Outcome OR 95% CI P value n OR 95% CI P value n

Preconception maternal mood

Stress in life affected health (5 levels)

1.10 0.98-1.24 0.093 2956 1.08 0.96-1.23 0.22 2548

Stress in daily living in the past 4 weeks (5 levels)

1.13 1.01-1.28 0.039 2951 1.12 0.99-1.28 0.072 2546

Psychological distress ascertained by GHQ-12 (no/yes)

1.21 0.85-1.73 0.30 1694 1.24 0.84-1.83 0.28 1419

Postnatal maternal mood between delivery and age 6 months

Edinburgh Postnatal Depression Score

1.01 0.99-1.03 0.28 2816 1.01 0.99-1.04 0.26 2431

Edinburgh Postnatal Depression Score ≥13

1.13 0.87-1.48 0.35 2816 1.12 0.84-1.49 0.44 2431

Between delivery and infant age 6 months experienced episodes of:

Feeling sad, depressed or gloomy for most of day (yes/no)

1.33 0.97-1.83 0.08 1713 1.40 1.00-1.96 0.048 1646

Unable to find pleasure in things normally enjoy (yes/no)

1.34 0.95-1.87 0.09 1660 1.26 0.88-1.80 0.20 1596

Lost interest in things normally enjoy (yes/no)

1.27 0.90-1.79 0.17 1660 1.26 0.88-1.79 0.22 1596

Feeling tired or worn out (yes/no)

1.07 0.72-1.61 0.73 1660 1.01 0.67-1.54 0.95 1596

Less energy than usual (yes/no)

1.35 0.89-2.06 0.16 1660 1.26 0.81-1.94 0.30 1596

*Adjusted for maternal age at birth, education, smoking in pregnancy, parity and eczema, and infant sex, gestational age at birth, season of birth and breastfeeding duration

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Table 4. Maternal stress/mood preconception and postnatally in relation to infant atopic eczema at age 12 months.

Unadjusted Adjusted *

Outcome OR 95% CI P value n OR 95% CI P value n

Preconception maternal mood


1.21 1.08-1.35 0.001 2871 1.21 1.07-1.37 0.002 2448


1.16 1.03-1.30 0.014 2867 1.14 1.00-1.29 0.046 2447

Psychological distress ascertained by GHQ-12 (no/yes)

1.43 1.00-2.04 0.044 1629 1.37 0.93-2.01 0.11 1340

Postnatal maternal mood between delivery and age 6 months

Edinburgh Postnatal Depression Score

1.02 1.00-1.04 0.045 2721 1.02 1.00-1.05 0.041 2330

Edinburgh Postnatal Depression Score >13

1.09 0.84-1.42 0.52 2721 1.08 0.82-1.44 0.58 2330

Between delivery and infant age 6 months experienced episodes of:

Feeling sad, depressed or gloomy for most of day (yes/no)

1.47 1.06-2.04 0.022 1621 1.52 1.08-2.13 0.016 1574

Unable to find pleasure in things normally enjoy (yes/no)

1.54 1.09-2.18 0.013 1569 1.55 1.08-2.20 0.016 1524

Lost interest in things normally enjoy (yes/no)

1.56 1.11-2.21 0.011 1569 1.57 1.10-2.24 0.013 1524

Feeling tired or worn out (yes/no)

1.51 0.95-2.40 0.08 1569 1.52 0.95-2.42 0.08 1524

Less energy than usual (yes/no)

1.75 1.09-2.79 0.020 1569 1.68 1.05-2.70 0.032 1524


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Table 5 Maternal preconception stress and postnatal mood in relation to infant atopic eczema at ages 6 and 12 months

OR 95% CI P value n

Infant atopic eczema age 6 months 2429

Preconception


1.04 0.91-1.20 0.57


1.09 0.94-1.25 0.24

Postnatal

EPDS 1.01 0.98-1.03 0.48

Infant atopic eczema age 12 months 2329

Preconception


1.80 1.03-1.35 0.015


1.07 0.93-1.22 0.34

Postnatal

EPDS 1.01 0.99-1.04 0.24


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